METHODS FOR CONTROLLING SEIZURES BY MANIPULATING THE LEVELS OF MICRORNA-211 (miR-211) IN THE BRAIN

Abstract

Method for controlling for the appearance of seizures in the mammalian brain comprising modifying the abundance of a specific miRNA-miR-211, for uses in preventing seizures and providing a model system to examine the effect of a drug or a treatment to seizures.

1 . A method of treating a human or a non-human mammal subject suffering from:
 brain injury, concussion, or disruption of the blood brain barrier   the method comprising the step of:
 (i) introducing into the brain of said human or non-human subject an oligonucleotide with the nucleic acid sequence of miR-211 
   
     
     
         2 . The method of  claim 1 , wherein said introducing into the brain of said human or non-human subject an oligonucleotide is done by either:
 (a) administering a miR-211 oligonucleotide mimetic to the bloodstream of said human or non-human subject, or   (b) administering a miR-211 oligonucleotide mimetic into—or to the proximity of—the brain of said human or non-human subject.   
     
     
         3 . The method of  claim 1 , wherein said human or a non-human mammal subject is suffering from disruption of the blood brain barrier following physical trauma to the head. 
     
     
         4 . The method of  claim 1 , wherein said human or a non-human mammal subject suffering from disruption of the blood brain barrier following neuro-inflammatory or a neuro-infectious Disease or following Acute Ischemic Stroke. 
     
     
         5 . The method of  claim 2 , wherein said mimetic molecule is selected from a group consisting of RNA, locked nucleic acid (LNA), 2-0-methyl-blocked, Morpholino and phosphorothioate oligonucleotides. 
     
     
         5 . The method of  claim 2 , wherein said oligonucleotide is selected from the group consisting of: SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 3, SEQ ID No. 4, SEQ ID No. 5, SEQ ID No. 6. 
     
     
         6 . The method of  claim 2 , wherein said introducing into the brain of said human or non-human subject an oligonucleotide with the nucleic acid sequence of miR-211 is done by administering a miR-211 oligonucleotide mimetic to the bloodstream of said human or non-human subject. 
     
     
         7 . The method of  claim 6 , wherein the blood brain-barrier of said human or non-human subject is compromised or disrupted. 
     
     
         8 . A method of Anti-epileptogenic intervention for treating a human or non-human subject expected to develop epileptogenesis, the method comprising the step of:
 (i) introducing into the brain of said human or non-human subject an oligonucleotide with the nucleic acid sequence of miR-211, by either:
 (a) administering a miR-211 oligonucleotide mimetic into—or to the proximity of—the brain of said human or non-human subject, or 
 (b) administering a miR-211 oligonucleotide mimetic to the bloodstream of said ‘human or non-human subject’, wherein the human or non-human subject is suffering from disruption of the blood brain barrier. 
   
     
     
         9 . The method of  claim 8 , wherein said introducing into the brain of said human or non-human subject an oligonucleotide is following (and within 1 month of) a medical event or condition selected from the group consisting of: physical trauma to the head, Acute Ischemic Stroke, status epilepticus, or neuro-inflammatory disruption of the blood brain barrier. 
     
     
         10 . The method of  claim 8 , wherein introducing into the brain of said human or non-human subject an oligonucleotide is done by administering a miR-211 oligonucleotide mimetic to the bloodstream of said human or non-human subject, and wherein the human or non-human subject is suffering from disruption of the blood brain barrier. 
     
     
         11 . The method of  claim 8 , wherein introducing into the brain of said human or non-human subject an oligonucleotide is done by administering a miR-211 oligonucleotide mimetic into—or to the proximity of—the brain of said human or non-human subject. 
     
     
         12 . The method of  claim 10 , wherein said mimetic molecule is selected from a group consisting of: RNA, locked nucleic acid (LNA), 2-O-methyl-blocked, Morpholino and phosphorothioate oligonucleotides. 
     
     
         13 . The method of  claim 10 , wherein said oligonucleotide is selected from the group consisting of: SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 3, SEQ ID No. 4, SEQ ID No. 5, SEQ ID No. 6. 
     
     
         14 . A method of treating or reducing the likelihood of the development or occurrence of seizures in an mammal subject, suffering from a condition characterized by expression changes in the rain of TGFBR2 pathway genes or of TGF signaling, the method comprising the step of:
 (i) introducing into the brain of said human or non-human subject an oligonucleotide with the nucleic acid sequence of miR-211, by either:
 (a) administering a miR-211 oligonucleotide mimetic into—or to the proximity of—the brain of said human or non-human subject, or 
 (b) administering a miR-211 oligonucleotide mimetic to the bloodstream of said human or non-human subject, wherein the human or non-human subject is suffering from disruption of the blood brain barrier. 
   
     
     
         15 . The method of  claim 14  wherein said oligonucleotide is selected from the group consisting of: SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 3, SEQ ID No. 4, SEQ ID No. 5, SEQ ID No. 6.